31 August 2021
Randomized Phase II Trial of Vincristine-Irinotecan With or Without Temozolomide, in Children and Adults With Relapsed or Refractory Rhabdomyosarcoma: A European Paediatric Soft tissue Sarcoma Study Group and Innovative Therapies for Children With Cancer Trial.
The VIT-0910 trial was the first study of the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) to focused on relapsed or refractory RMS. This trial randomly assigned patients age 6 months to 50 years with relapsed/refractory RMS to 21-day cycles of VI with and without temozolomide. The control arm (which only received VI) was selected based on results of the ARST0121 trial, which found a shorter regimen of VI had the same good efficacy as VI administered in a protracted schedule among adults and children with relapsed/refractory RMS.
The goal of the trial was to help better define the standard chemotherapy regimen for relapsed cases, to which novel agents could be added or other innovative therapies compared. The primary endpoint was overall response rate after two cycles of chemotherapy. Secondary endpoints were progression-free survival, OS, and adverse events (AEs).
Results indicated a benefit of the combination chemotherapy, with an overall response rate of 44% in the VI plus temozolomide (VIT) arm (24 of 55 evaluable patients) and 31% in the VI arm (18 of 58 patients) for patients with relapsed RMS. OS was significantly better with VIT (adjusted HR 0.55), with consistent results for reduction in risk of disease progression or relapse.
Despite these benefits, toxicity was a concern in patients treated with VIT, with 98% experiencing grade 3 or higher AEs, compared with 78% of patients receiving VI only. Serious treatment-related AEs were also more common in VIT treatment than control (38% vs. 19%).
Based on results from this trial, VIT combination therapy is now considered in Europe to be the new preferred treatment for patients with relapsed RMS who have previously received an alkylating agent.
Building on the success of this trial, the EpSSG have implemented a multi-arm, multistage study exploring frontline treatment of relapsed RMS (NCT04625907) in which VIT will be the control arm for relapsed disease. The increased toxicity with VIT in the VIT-0910 trial raises the question of whether it will be possible to add new targeted therapy or immunotherapy to this chemotherapy. The first new combination to be tested will be VI with the tyrosine kinase inhibitor regorafenib.
The goal of the trial was to help better define the standard chemotherapy regimen for relapsed cases, to which novel agents could be added or other innovative therapies compared. The primary endpoint was overall response rate after two cycles of chemotherapy. Secondary endpoints were progression-free survival, OS, and adverse events (AEs).
Results indicated a benefit of the combination chemotherapy, with an overall response rate of 44% in the VI plus temozolomide (VIT) arm (24 of 55 evaluable patients) and 31% in the VI arm (18 of 58 patients) for patients with relapsed RMS. OS was significantly better with VIT (adjusted HR 0.55), with consistent results for reduction in risk of disease progression or relapse.
Despite these benefits, toxicity was a concern in patients treated with VIT, with 98% experiencing grade 3 or higher AEs, compared with 78% of patients receiving VI only. Serious treatment-related AEs were also more common in VIT treatment than control (38% vs. 19%).
Based on results from this trial, VIT combination therapy is now considered in Europe to be the new preferred treatment for patients with relapsed RMS who have previously received an alkylating agent.
Building on the success of this trial, the EpSSG have implemented a multi-arm, multistage study exploring frontline treatment of relapsed RMS (NCT04625907) in which VIT will be the control arm for relapsed disease. The increased toxicity with VIT in the VIT-0910 trial raises the question of whether it will be possible to add new targeted therapy or immunotherapy to this chemotherapy. The first new combination to be tested will be VI with the tyrosine kinase inhibitor regorafenib.
